Homology Based Structure Predictions Hemochromatosis

Hemochromatosis>>Task 4: Homology based structure predictions

Riddle of the task

After endless battles and deadly traps you have finally reached the tomb's final chamber. As you enter it you notice that there is no sign of the treasures that were promised by the old map you found months ago. Suddenly you hear a loud noise behind you and a solid wall of stone blocks the only entrance into the room. You are trapped! You look around and notice something on the walls. On the left wall are four runes in an ancient language. Luckily its the same language as the notes on the map you deciphered and they translate into four single letters:

• C N O I

On the opposite wall you can see four simple symbols:

• a triangle
• a square
• a circle
• and a diamond (dt. Raute)

After further investigation you notice that the four symbols can be pushed into the wall, but you don't know what would happen and which one(s) to push.

What do you do?

Some hints:

• You only have to push one button and only once.

Short Task Description

Detailed description: Homology based structure predictions

Protocol

A protocol with a description of the data acquisition and other scripts used for this task is available here.

PDB templates

In order to find templates for our models we performed several searches for homologs with COMA and HHPred. We also reused the sequences from Task 2. However none of these methods yielded homologs with a sequence identity above 40% (except 1a6z which is HFE itself) that could be mapped to a PDB structure. The best results for COMA and HHPred are listed in <xr id="coma_t"/> and <xr id="hhpred_t"/> respectively. Therefore we could not generate models with a sequence identity above 80% and the 40%-80% range was limited to its lower bound.

<figtable id="coma_t">

TODO: COMA: Top10 (e-Value) sorted by Identities.

PDB ID	e-Value	Identities	Positives
1a6z_A	1.00E-63	100%	100%
1t7v_A	1.20E-63	34%	62%
3nwm_A	1.60E-57	30%	57%
1frt_A	4.90E-65	28%	66%
2wy3_A	2.80E-63	26%	66%
3ov6_A	2.70E-55	20%	67%
1u58_A	1.00E-54	19%	59%
3d2u_A	7.50E-60	16%	70%
3dbx_A	9.70E-59	16%	71%
3it8_D	3.40E-52	15%	65%

</figtable>

<figtable id="hhpred_t">

TODO: HHpred: Top10 (e-Value) sorted by Identities.

PDB ID	e-Value	Identities	Similarity
1a6z_A	1.80E-69	100%	1.623
1k5n_A	2.80E-68	40%	0.725
1s7q_A	5.80E-78	37%	0.655
1t7v_A	7.40E-68	36%	0.702
3p73_A	1.10E-69	35%	0.638
3bev_A	1.00E-69	34%	0.684
2yf1_A	2.40E-74	32%	0.617
1zs8_A	7.30E-68	30%	0.553
2wy3_A	3.30E-68	29%	0.496
1cd1_A	1.60E-67	21%	0.394

</figtable>

Model generation

Modeller

Evaluation

<figtable id="scores_native">

TODO: NATIVE.

Model	Common residues	TM-Score	GDT-TS-Score	GDT-HA-Score	TM-Align	Nr. of atoms	Weighted RMSd
1K5N_2d	272	0.1686	0.0846	0.0487	0.83298	272	2.200
1K5N_simple	272	0.1649	0.0846	0.0506	0.83358	272	2.325
1ZS8_2d	272	0.1698	0.0827	0.0432	0.85494	272	1.642
1ZS8_simple	272	0.1550	0.0790	0.0423	0.79841	271	2.302
2IAD_2d	272	0.1725	0.0836	0.0460	0.49103	269	2.166
2IAD_simple	272	0.1337	0.0607	0.0349	0.40162	272	3.705
3DBX_2d	272	0.1742	0.0892	0.0496	0.81698	267	2.374
3DBX_simple	272	0.1684	0.0882	0.0496	0.86512	267	1.524

</figtable>

<figtable id="scores_complex">

TODO: COMPLEX.

Model	Common residues	TM-Score	GDT-TS-Score	GDT-HA-Score	TM-Align	Nr. of atoms	Weighted RMSd
1K5N_2d	272	0.1674	0.0800	0.0469	0.85238	272	1.986
1K5N_simple	272	0.1638	0.0800	0.0478	0.83836	272	2.142
1ZS8_2d	272	0.1715	0.0827	0.0450	0.86026	272	1.720
1ZS8_simple	272	0.1550	0.0790	0.0414	0.82124	271	2.059
2IAD_2d	272	0.1706	0.0836	0.0441	0.48549	269	2.279
2IAD_simple	272	0.1318	0.0653	0.0358	0.40088	272	3.655
3DBX_2d	272	0.1737	0.0873	0.0487	0.83662	269	2.088
3DBX_simple	272	0.1687	0.0901	0.0515	0.86877	269	1.492

</figtable>